Study of Durvalumab Given With Chemotherapy, Durvalumab in Combination With Tremelimumab Given With Chemotherapy, or Chemotherapy in Patients With Unresectable Urothelial Cancer
- Conditions
- Unresectable Locally Advanced Urothelial CancerMetastatic Urothelial Cancer
- Interventions
- Registration Number
- NCT03682068
- Lead Sponsor
- AstraZeneca
- Brief Summary
This is a randomized, open-label, controlled, multi-center, global Phase III study to determine the efficacy and safety of combining durvalumab ± tremelimumab with standard of care (SoC) chemotherapy (cisplatin + gemcitabine or carboplatin + gemcitabine doublet) followed by durvalumab monotherapy versus SoC alone as first-line chemotherapy in patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1246
- Patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra)
- Patients who have not been previously treated with first-line chemotherapy. Patients who have received prior definitive chemoradiation, adjuvant or neoadjuvant treatment for locally advanced disease are eligible provided that progression to locally advanced or metastatic disease has occurred >12 months from the last therapy [for chemoradiation and adjuvant treatment] or >12 months from the last surgery [for neoadjuvant treatment].
- At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline.
- World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment
- Adequate organ and marrow function as defined in the protocol
- Life expectancy ≥12 weeks in the opinion of the investigator
- Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.
Key
- Prior exposure to immune-mediated therapy (with exclusion of Bacillus Calmette Guerin), including but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD L1, or anti-PD-L2 antibodies, except therapeutic anticancer vaccines, which are permitted. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
- No severe concomitant condition that requires immunosuppression medication
- Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
- Patients who may be eligible for or are being considered for radical resection during the course of the study.
- Any medical contraindications to platinum (cisplatin or carboplatin) based doublet chemotherapy and/or known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Durvalumab in Combination with SoC Chemotherapy Durvalumab Durvalumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks. All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: * cisplatin+ gemcitabine * If the patient is cisplatin-ineligible, carboplatin + gemcitabine Durvalumab in Combination with SoC Chemotherapy Cisplatin + Gemcitabine Durvalumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks. All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: * cisplatin+ gemcitabine * If the patient is cisplatin-ineligible, carboplatin + gemcitabine Durvalumab in Combination with SoC Chemotherapy Carboplatin + Gemcitabine Durvalumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks. All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: * cisplatin+ gemcitabine * If the patient is cisplatin-ineligible, carboplatin + gemcitabine Durvalumab in Combination with Tremelimumab+SoC Chemotherapy Durvalumab Durvalumab and Tremelimumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks Tremelimumab will be provided for 4 cycles. All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: * cisplatin+ gemcitabine * If the patient is cisplatin-ineligible, carboplatin + gemcitabine Durvalumab in Combination with Tremelimumab+SoC Chemotherapy Tremelimumab Durvalumab and Tremelimumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks Tremelimumab will be provided for 4 cycles. All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: * cisplatin+ gemcitabine * If the patient is cisplatin-ineligible, carboplatin + gemcitabine Durvalumab in Combination with Tremelimumab+SoC Chemotherapy Cisplatin + Gemcitabine Durvalumab and Tremelimumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks Tremelimumab will be provided for 4 cycles. All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: * cisplatin+ gemcitabine * If the patient is cisplatin-ineligible, carboplatin + gemcitabine Durvalumab in Combination with Tremelimumab+SoC Chemotherapy Carboplatin + Gemcitabine Durvalumab and Tremelimumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks Tremelimumab will be provided for 4 cycles. All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: * cisplatin+ gemcitabine * If the patient is cisplatin-ineligible, carboplatin + gemcitabine SoC Chemotherapy Cisplatin + Gemcitabine Patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: * cisplatin+ gemcitabine * If the patient is cisplatin-ineligible, carboplatin + gemcitabine SoC Chemotherapy Carboplatin + Gemcitabine Patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles: * cisplatin+ gemcitabine * If the patient is cisplatin-ineligible, carboplatin + gemcitabine
- Primary Outcome Measures
Name Time Method Overall Survival (OS) approximately 5 years OS is defined as the time from the date of randomization until death due to any cause
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) approximately 5 years Additional analysis beyond the primary endpoint
Overall Survival at 24 months (OS24) 24 months The OS24 will be defined as the Kaplan-Meier estimate of OS at 24 months
Progression Free Survival (PFS) approximately 5 years PFS (per RECIST 1.1) will be defined as the time from the date of randomization until the date of first objective disease progression or death
Alive and Progression Free Survival at 12 months (APF12) 12 months The APF12 will be defined as the Kaplan-Meier estimate of PFS (per RECIST 1.1) at 12 months
Objective Response Rate (ORR) approximately 5 years ORR (per RECIST 1.1) is defined as the number (%) of patients with at least 1 visit response of complete response or partial response and will be based on a subset of all randomized patients
Duration of Response (DoR) approximately 5 years DoR (per RECIST 1.1) will be defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression
Disease Control Rate (DCR) approximately 5 years DCR is defined as the proportion of subjects with the best overall response of complete response, partial response or stable disease per RECIST 1.1
Time from randomization to second (PFS2) approximately 5 years PFS2 will be defined as the time from the date of randomization to the earliest of the progression events subsequent to that used for the PFS endpoint or death
To assess disease-related symptoms, physical functioning, and other Health-related quality of life approximately 5 years Collection of patient reported outcome questionnaires
Trial Locations
- Locations (1)
Research Site
🇻🇳Ho Chi Minh, Vietnam